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Lycopene Regulates Macrophage Immune Response through the Autophagy Pathway Mediated by RIPK1
Yupei Yao1, Xiaoran Liu1, Xiaoyan Niu1
1Hebei Key Laboratory of Public Health Safety, Ministry of Education & College of Public Health, Hebei University, Baoding 071002, China.
Abstract:
The effects of lycopene (LP) on macrophage immune responses were evaluated in this study. Compared with the control treatment, LP treatment significantly increased cell vitality, phagocytic activity, and chemokine production in RAW264.7 cells. Additionally, compared with the control treatment, 4 μM LP treatment significantly activated autophagy, enhanced mitochondrial membrane potential, and upregulated receptor-interacting protein kinase 1 (RIPK1), while necrostatin-1 significantly reversed these effects of LP. Furthermore, compared with that in the control group, RIPK1 was significantly upregulated in the 4 μM LP and 4 μM LP + spautin-1 groups, whereas p-mTOR levels were reduced. More importantly, compared with that in the control group, p62 was significantly downregulated, and Beclin1, LC3-II, and Atg7 were upregulated in the 4 μM LP group, while spautin-1 significantly reversed these effects of LP. These results confirm that LP activates the mTOR/Beclin1/LC3/p62 autophagy signaling pathway through RIPK1, thereby enhancing the immune response of macrophages.
Insights
Lycopene (LP) boosts macrophage immune responses by enhancing cell vitality and activity. It activates autophagy via the RIPK1-mTOR pathway, improving overall immune function.
Area of Science:
- Immunology
- Cell Biology
- Nutritional Science
Background:
- Macrophages are crucial immune cells involved in host defense.
- Dietary compounds can modulate macrophage function and immune responses.
- Lycopene, a carotenoid, possesses antioxidant and potential immunomodulatory properties.
Purpose of the Study:
- To investigate the effects of lycopene (LP) on macrophage immune responses.
- To elucidate the underlying molecular mechanisms, including autophagy activation and signaling pathways.
Main Methods:
- Utilized RAW264.7 macrophage cell line.
- Assessed cell vitality, phagocytic activity, and chemokine production.
- Analyzed autophagy markers (p62, Beclin1, LC3-II, Atg7), mitochondrial membrane potential, and key signaling proteins (RIPK1, p-mTOR).
- Employed specific inhibitors (necrostatin-1, spautin-1) to dissect signaling pathways.
Main Results:
- Lycopene significantly increased macrophage cell vitality, phagocytosis, and chemokine production.
- LP treatment activated autophagy, enhanced mitochondrial membrane potential, and upregulated RIPK1.
- The mTOR/Beclin1/LC3/p62 autophagy pathway was activated by LP through RIPK1.
- Inhibitors reversed the effects of LP, confirming the involvement of RIPK1 and autophagy.
Conclusions:
- Lycopene enhances macrophage immune responses by activating the RIPK1-dependent mTOR/Beclin1/LC3/p62 autophagy pathway.
- These findings highlight lycopene's potential as an immunomodulatory agent.
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